Abstract P3-07-26: Anti-cancer activity of naturally formulated Trigonella foenum graecum (Fenugreek) PLGA hyaluronic acid-coated nanoparticles for treatment of breast cancer cell lines
Authors: Islam Yahiya, Rana Saeed, Ahmed Sultan
Journal: Cancer Research (2023)

Abstract There are several growing evidences of anticancer complementary and alternative medicines worldwide. Trigonella foenum graecum (Fenugreek) is traditionally applied to treat several disorders such as diabetes, inflammation, and gastrointestinal ailments. Previously, we reported that Fenugreek has anticancer properties against liver cancer due to its active beneficial chemical constituents. Herein, Fenugreek-loaded poly (l-lactic-co-glycolic acid) (PLGA) hyaluronic acid (HA)-coated nanoparticles have been formulated to improve and enhance the anticancer potential of Fenugreek against human breast cancer cell lines. The cytotoxic effects, physicochemical characterization in vitro and pharmacodynamic study of optimized formulation of the FCE-loaded (PLGA)-(HA)-coated nanoparticles in vivo were investigated in (ER-positive) and (triple-negative), breast cancer cell lines, ZR-75-1 and MDA-MB-231, respectively. The particle size, PDI, zeta potential, entrapment efficiency, and loading capacity of FCE-loaded nanoparticles were 188.5 ± 3.1 d.nm, 0.198 ± 0.114, −.118 mV, 38.41 ± 1.4%, and 6.37 ± 1.08%, respectively. The in vitro cytotoxicity study of FCE-loaded NPs by Wst-1 proliferation assay on both tested breast cancer cell lines showed an anti-cancer activity after 48 h of treatment in a dose-dependent manner. Furthermore, the anticancer effect of FCE-loaded nanoparticles was examined by the morphological cell changes, histone release, caspase-3 activity, and modulation of the oncogenic signal pathways of m-tor, β-catenin, cyclin D-1 and STAT3 that are constitutively active in wide variety of breast cancer cell lines which in turn could be important as therapeutic targets in breast cancer. 66 μg/mL FCE-loaded PLGA nanoparticles induced 67.3% apoptosis in both tested cell lines after 48 h that was associated with increased expression of caspase 3, Bax, Bak, p53, and cell cycle arrest at G0/G1 in a time-and dose-dependent manner compared to unloaded-nanoparticles or untreated cells. Moreover, there were significant inhibition in m-tor, β-catenin, cycline-D1, and STAT3 expression levels in both tested cell lines compared to un-loaded-nanoparticles or untreated cells. All in all, our results showed that the formulated FCE-loaded (PLGA)-(HA)-coated nanoparticles induced apoptosis in both ER-positive and triple-negative breast cancer cell lines respectively by increase the expression of pro-apoptotic genes and inhibited several oncogenic genes that might hold a promise for the complementary therapy for human breast cancer. Citation Format: Islam Yahiya, Rana Saeed, Ahmed Sultan. Anti-cancer activity of naturally formulated Trigonella foenum graecum (Fenugreek) PLGA hyaluronic acid-coated nanoparticles for treatment of breast cancer cell lines [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-26.